PROJECT ABSTRACT: This Bioengineering Research Partnership (BRP) will deliver comprehensive measurements of 3D deformation of the human brain, in males and females of different ages, caused by skull motions of different types, directions, and frequency content. We will then develop methods to use these data to build and evaluate computer models of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE). Such data and methods to exploit them will enable the next generation of computer models to predict the chronic effects of repeated head impacts. We will thus address the un-met need for data and data-driven methods to guide and evaluate computer models of brain injury. We can now measure 3D deformation throughout the brain caused by (i) harmonic skull motion (using MR elastography, MRE), and (ii) impulsive linear and angular skull acceleration (using tagged MRI). These measurements can quantify the mechanical vulnerability of the brain, which will be of great value to three classes of end-users: (A) developers of computer models, who need these quantitative data and tools to build and assess simulations; (B) makers of protective equipment, who need data to rationally design helmets and sensors; and (C) clinicians and TBI researchers, who need data to understand injury mechanisms, design relevant animal studies, and improve therapies. We propose three tasks: Task 1: Measure brain deformation by MRE during harmonic skull motion of different directions and frequencies; Task 2: Measure brain deformation by tagged MRI during impulsive skull motion of different directions/durations; Task 3: Develop and demonstrate data-driven tools to improve computer models of 3D brain deformation. MR-based measurements will be performed in male and female subjects of different ages to illuminate the effects of gender and age on the brain?s mechanical vulnerability. Successful completion of these tasks will provide: (i) new quantitative data that captures age/sex differences in brain mechanics using harmonic motion in a robust and accessible imaging modality (MRE), (ii) new data to quantify brain deformation under mild impulsive loading, and (iii) new capability to accurately simulate brain deformation, and to evaluate and interpret model predictions. This partnership involves researchers with distinct expertise and capabilities at four sites. Washington University; the Henry Jackson Foundation; Johns Hopkins University; and the University of Delaware. The team will use novel pulse sequences to efficiently perform 3D MRE at multiple excitation frequencies and directions, and will apply new analysis methods to find natural frequencies and modes of brain motion from tagged MRI. The unprecedented data from this project, relating brain deformation to skull motion in subjects of different age and sex, will be exploited to provide a new framework for modeling the effects of chronic impact on the brain.